Lactate compartmentation in hippocampal slices: evidence for a transporter.
Lactic acid accumulation has been implicated in the evolution of brain damage after ischemia. Since compartmentation of lactate may play a role in acid-base balance, lactate release from gerbil hippocampal slices was examined during a number of metabolic stresses including elevated [K+]e, ischemia, anoxia, and aglycemia. Slices were preincubated for 1 hr in artificial cerebrospinal fluid (ACSF) equilibrated with 95% O2/5% CO2 (pH 7.4 at 37 degrees C) and then transferred to tubes containing 300 microliters of test medium. The rate of lactate release in control slices was 9.64 nmol/min/mg protein and increased 2.6- and 3.2-fold in the presence of 60 mM potassium and anoxia, whereas the rate of lactate release was decreased by 50 and 25% during ischemia and aglycemia. Lactate release was temperature dependent and was only minimally influenced by removing Ca2+ or by adding 5 mM d-lactate to the ACSF. In contrast, pyruvate inhibited lactate release with an apparent Ki of 2.4 mM. The results suggest that lactate can be released from cells via a saturable and stereospecific lactate transporter with an apparent Km of 10.7 mM and Vmax of 43.7 nmol/mg protein/min. Such a relatively high-capacity transporter system can rapidly equilibrate brain lactate but is probably not involved in regulating intracellular acid-base balance.
Assaf
H M
HM
Laboratory of Experimental Neurosurgery, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
Ricci
A J
AJ
Whittingham
T S
TS
LaManna
J C
JC
Ratcheson
R A
RA
Lust
W D
WD
D000255:Adenosine Triphosphate / Q000134:cerebrospinal fluid; D000818:Animals; D001692:Biological Transport; D002545:Brain Ischemia / Q000378:metabolism*; D002451:Cell Compartmentation; D005849:Gerbillinae; D006624:Hippocampus / Q000378:metabolism*; D002534:Hypoxia, Brain / Q000378:metabolism*; D007700:Kinetics; D007773:Lactates / Q000378:metabolism*; D011339:Probenecid / Q000134:cerebrospinal fluid; D011773:Pyruvates / Q000134:cerebrospinal fluid
D007773:Lactates; D011773:Pyruvates; D000255:Adenosine Triphosphate; D011339:Probenecid